Expression, subcellular localisation, and possible roles of dipeptidyl peptidase 9 (DPP9) in murine macrophages

Abstract

Dipeptidyl peptidase 9 (DPP9) is a peptidase of the DPPIV gene family, and its role in immune responses has been reported. In this study, we compared the messenger RNA expression profile of DPP9 to that of the related DPP8 and DPPIV in murine haematopoietic and lymphatic tissues. A similar order of expression levels was observed for all 3 peptidases: peritoneal macrophages < bone marrow < spleen ≤ lymph nodes. Also, we examined the subcellular localisation of DPP9 and its possible role(s) in J774 cell line of macrophage origin. DPP9 was dominantly expressed intracellularly. DPPIV-like enzymatic activity was mostly present in cytoplasm, but also in cell membranes and organelles/vesicles. Decreased expression of DPP9 was observed upon activation of J774 cells by combined treatment with interferon gamma and lipopolysaccharide. Changes induced by DPP9 gene silencing in J774 cells suggest possible role of DPP9 in regulation of proliferation and activation status. The colocalisation of DPP9 with endocytosed DQ-OVA demonstrated in endosomes of J774 cells might suggest the role of DPP9 in peptide processing within endosomal/vesicular compartment.

The effect of CD26‐deficiency on dipeptidyl peptidase 8 and 9 expression profiles in a mouse model of Crohn's disease

“…That would be one possible explanation why DP9 and especially DP8 are abundant in serum. Furthermore, DP9 was observed near the ruffling membrane upon stimulation of the hepatocyte‐derived carcinoma cells and a discrete surface localization of DP9 on the membrane surface of the cells of macrophage origin was very recently demonstrated by Zapletal et al who hypothesized that DP9 could transiently localize on the plasma membrane as a part of the exosomes trafficking. Our results back such an assumption although describing the exact mechanism on how DP8 and DP9 are transferred outside the cell in vivo is the coming challenge that should be investigated.…”

“…For that reason, our aim is to determine whether experimental colitis induces any changes in the comparative expression patterns and/or enzyme activity of DP8 and DP9 under CD26 deficiency. Additionally, despite the fact that DP8 and DP9 are presumed to be predominantly intracellularly localized, certain evidence point to the possibility of their routing to some of the secretion pathways . Therefore, our second aim was to determine if these two proteins exist in mouse serum and whether their concentration and activity are subjected to change caused by colitis development.…”

“…Additionally, despite the fact that DP8 and DP9 are presumed to be predominantly intracellularly localized, certain evidence point to the possibility of their routing to some of the secretion pathways. 16,18 Therefore, our second aim was to determine if these two proteins exist in mouse serum and whether their concentration and activity are subjected to change caused by colitis development.…”

New insights into the role of dipeptidyl peptidase 8 and dipeptidyl peptidase 9 and their inhibitors

“…Soluble DPP8 and DPP9 have also been found in mouse serum ( Buljevic et al, 2018 ), suggesting that they could somehow be secreted outside the cell and function by their enzyme activity and/or by interactions with extracellular molecules. In addition, DPP9 in macrophage cells may be involved in antigen presentation and temporarily located on the plasma membrane surface ( Zapletal et al, 2017 ). In tumor cells and fibroblasts, DPP9 may participate in cell adhesion and migration and locates adjacent to the edge of the plasma membrane ( Zhang et al, 2015b ; Gabrilovac et al, 2017 ).…”

A novel function of DPP9 in DNA damage repair via BRCA2 regulation

“…DPP9 protein expression has also been found in human and murine macrophages (Okondo et al, 2016;Waumans et al, 2015;Zapletal et al, 2017), emphasizing the role of DPP9 in the immune system, which is one of the main studied functions of DPP9 until today (see point 1.4.4.5.). Besides the lymphoid cells, the epithelial cells also manifest DPP9 expression in organs such as lung, liver, and intestine.…”